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Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging
Published on: July 1, 2021
Nucleophosmin3 carried by small extracellular vesicles contribute to white adipose tissue browning
Yan Zhang1,2,3, Mei Yu4,5,6, Jia Dong7,1,2,8
1National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, China.
Background:
Browning of white adipose tissue (WAT) is a particularly appealing target for therapeutics in the treatment of obesity and related metabolic diseases. Although small extracellular vesicles (sEVs) released from adipose tissue (sEVs-AT) have emerged as novel player that regulate systemic metabolism by connecting different organs, the role of specific contents in sEVs-AT played in WAT browning has not been clarified.
Results:
We revealed Nucleophosmin3 (NPM3), which was mainly transferred by sEVs derived from brown adipose tissue (sEVs-BAT), was served as a batokine that could induce WAT browning by regulating the stability of PRDM16 mRNA. sEVs-BAT enhanced the expressions of browning related genes in 3T3-L1 preadipocytes and WAT while knocking down of NPM3 in BAT impaired sEVs-BAT mediated WAT browning and weight loss in obesity.
Conclusion:
These data provided new insight into the role of NPM3 in regulating the browning of WAT. Our study indicated that a supplement of sEVs-BAT might represent a promising therapeutic strategy to promote thermogenesis and energy expenditure in the future.
Insights
Small extracellular vesicles from brown adipose tissue (sEVs-BAT) transfer Nucleophosmin3 (NPM3), a key factor promoting white adipose tissue (WAT) browning. Supplementing sEVs-BAT may offer a therapeutic strategy for obesity and metabolic diseases.
Area of Science:
- Metabolic Regulation
- Adipose Tissue Biology
- Extracellular Vesicle Research
Background:
- White adipose tissue (WAT) browning is a therapeutic target for obesity and metabolic diseases.
- Small extracellular vesicles (sEVs) from adipose tissue (sEVs-AT) are emerging regulators of systemic metabolism.
- The specific roles of sEVs-AT contents in WAT browning remain unclear.
Purpose of the Study:
- To investigate the role of specific contents within sEVs-AT in regulating WAT browning.
- To identify novel factors transferred by sEVs-BAT that influence adipose tissue metabolism.
Main Methods:
- Investigated Nucleophosmin3 (NPM3) transfer via sEVs derived from brown adipose tissue (sEVs-BAT).
- Assessed the impact of sEVs-BAT on browning-related gene expression in 3T3-L1 preadipocytes and WAT.
- Examined the effects of NPM3 knockdown in brown adipose tissue (BAT) on sEVs-BAT-mediated WAT browning and weight loss in an obesity model.
Main Results:
- Nucleophosmin3 (NPM3) was identified as a key cargo of sEVs-BAT, acting as a batokine.
- NPM3 transfer by sEVs-BAT induced WAT browning by enhancing PRDM16 mRNA stability.
- Knockdown of NPM3 in BAT abrogated the WAT browning and weight loss effects of sEVs-BAT in obesity.
Conclusions:
- NPM3 plays a crucial role in regulating WAT browning through sEV-mediated transfer.
- sEVs-BAT represents a promising therapeutic strategy for enhancing thermogenesis and energy expenditure.
- This study provides new insights into the molecular mechanisms of WAT browning and potential obesity treatments.
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